Allograft rejection and tumor immunity are generally considered to be manifestations of cell-mediated immune mechanisms of which cytotoxic T lymphocytes (CTL) are of major importance. Lymphoid cells are able to generate two kinds of CTL: Allogeneic and major histocompatibility complex (MHC)-restricted, hapten-specific (syngeneic). Whereas allogeneic CTL are thought to be important in allograft rejection, syngeneic CTL are thought to be of importance in autoimmunity and in surveillance against autologous neoplastic cells and against infections. Although the cellular interactions involved in the generation of syngeneic CTL remain ill-defined, it appears that the mechanism of generation of both kinds of CTL is dependent on non-B, Ia+ splenic adherent cells (SAC). This proposal will examine the SAC subpopulations, and their soluble products, needed for the generation of allogeneic vs syngeneic CTL, placing the comparisons on a quantitative basis whenever possible. In particular, experiments will be performed to examine the requirement for MHC homology between SAC and responding T cells. The Ia+ non-phagocytic subpopulations will be purified and examined for their antigen presenting function for both kinds of CTL. These experiments will also utilize the recently described finding that ultraviolet light (UV) irradiation, in vivo, depletes the Ia bearing SAC. The SAC subpopulations depleted by in vivo and in vitro UV irradiation will be determined. This approach may allow us to characterize the SAC subpopulation which produces the soluble mediator lymphocyte activating factor in interleukin 1(IL1). Moreover, attempts will be made to delineate the MHC-restrictions of the soluble factors IL1 and interleukin 2 (IL2) as well as the mechanisms by which IL1 enables T cells to elaborate IL2. This proposal will also attempt to examine the possible differences in antigen processing by SAC obtained from mice of different H-2 haplytypes. These studies will provide us with a better understanding of the comparative mechanisms involved in the generation of allogeneic and syngeneic CTL. Such an understanding is necessary for the eventual goal of manipulating these responses in vivo situations wherein it is desirable to enhance one type of CTL while inhibiting the other.